Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors

  • Nat Commun. 2021 Apr 1;12(1):2016. doi: 10.1038/s41467-021-22362-2.
Sho Iketani  1  2 ,  Farhad Forouhar  3 ,  Hengrui Liu  4 ,  Seo Jung Hong  5 ,  Fang-Yu Lin  6 ,  Manoj S Nair  1 ,  Arie Zask  7 ,  Yaoxing Huang  1 ,  Li Xing  6 ,  Brent R Stockwell  8  9 ,  Alejandro Chavez  10 ,  David D Ho  11  12
Affiliations
  • 1. Aaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, USA.
  • 2. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
  • 3. Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
  • 4. Department of Chemistry, Columbia University, New York, NY, USA.
  • 5. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
  • 6. WuXi AppTec, Cambridge, MA, USA.
  • 7. Department of Biological Sciences, Columbia University, New York, NY, USA.
  • 8. Department of Chemistry, Columbia University, New York, NY, USA. [email protected].
  • 9. Department of Biological Sciences, Columbia University, New York, NY, USA. [email protected].
  • 10. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA. [email protected].
  • 11. Aaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, USA. [email protected].
  • 12. Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA. [email protected].
PMID: 33795671 DOI: 10.1038/s41467-021-22362-2
Abstract

We report the identification of three structurally diverse compounds - compound 4, GC376, and MAC-5576 - as inhibitors of the SARS-CoV-2 3CL protease. Structures of each of these compounds in complex with the protease revealed strategies for further development, as well as general principles for designing SARS-CoV-2 3CL Protease Inhibitors. These compounds may therefore serve as leads for the basis of building effective SARS-CoV-2 3CL Protease Inhibitors.

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